Quinolinic Acid Responses during Interferon-α-Induced Depressive Symptomatology in Patients with Chronic Hepatitis C Infection - A Novel Aspect for Depression and Inflammatory Hypothesis

PLoS One. 2015 Sep 14;10(9):e0137022. doi: 10.1371/journal.pone.0137022. eCollection 2015.

Abstract

Background: The aim of this exploratory study is to gain for the first time a more comprehensive picture of the impact of changes of quinolinic acid concentrations on depressive symptomatology during and after IFN-α therapy.

Methods: The quinolinic acid concentrations of 35 HCV patients are examined in a prospective survey over the entire period of IFN-α treatment as well as three months later at six different times (baseline, one, three, six and nine months after the beginning of IFN-α treatment, and after the end of treatment).

Results: During IFN-α treatment Hamilton Depression Rating Scale scores rise significantly. At the same time there is greater activity of indoleamine 2,3-dioxygenase, with a resulting increase in plasma kynurenine concentrations. Compared to baseline values quinolinic acid concentrations increase significantly during therapy, reflecting an increased neurotoxic challenge. In addition, patients with higher scores in the Hamilton Depression Rating Scale at six and nine months after starting therapy show significantly higher levels of quinolinic acid concentration.

Conclusions: The increase of quinolinic acid during IFN-α therapy might contribute to depressive symptomatology through the neurotoxic challenge caused by quinolinic acid. Subsequently, our exploratory study results support the inflammatory hypothesis of depression. The awareness of relevant risk factors of IFN-α treatment-induced depression is essential to develop preventative treatment strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / adverse effects*
  • Antiviral Agents / therapeutic use
  • Depression / chemically induced*
  • Depression / metabolism
  • Female
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / metabolism
  • Hepatitis C, Chronic / psychology
  • Humans
  • Interferon-alpha / adverse effects*
  • Interferon-alpha / therapeutic use
  • Kynurenine / blood
  • Male
  • Middle Aged
  • Prospective Studies
  • Psychiatric Status Rating Scales
  • Quinolinic Acid / analysis*

Substances

  • Antiviral Agents
  • Interferon-alpha
  • Kynurenine
  • Quinolinic Acid

Grants and funding

This study was supported by a grant from the Pfizer Corporation Austria. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.